The isolation of discrete, sequence-defined genetic elements from complex genomic samples is an essential step in many genetic analysis protocols including, de novo sequencing, re-sequencing, gene expression, epigenetic state analyses, genetic variation discovery and scoring (e.g. SNPs and STRs). Defined sequence elements or fragments that share a common sequence element can be isolated using a common primer such as oligo dT to target the poly-A tails of messenger RNA (Chow et al., (1988) Anal. Biochem., 175; 63). Protocols to isolate and amplify defined mixtures of ragments from complex genomic samples currently rely upon defined primer pairs and some form of amplification protocol such as PCR, isothermal amplification or LCR. However, these method suffer significant limitations since the degree of multiplexing is generally limited to only 10 to 20 primer pairs which must be co-optimized for a given reaction condition. As a result, genetic analysis protocols that require the interrogation of a large number of sites or sequence elements within a complex sample mixture such as SNP genotyping or comparative genomic hybridization (CGH) have relied upon various genome complexity reduction methods that utilize various LCR, PCR and random priming techniques that are not element defined (Kinzler & Vogelstein, Nucleic Acids Res (1989) 17; 3645, Telenius et al., Genomics (1992) 13;1718, Kristjansson et al., Nature Genetics (1994) 6; 19, Lucito et al., Proc. Natl. Acad. Sci. USA (1998) 95; 4487, Kennedy et al., (2003), Nat. Biotechnol. 21;1233 & Bignell et al., (2004) Genome Research 14; 287).
What is needed is a convenient method for providing defined mixtures of nucleic acids from complex samples.